Background: The major house dust mite (HDM) allergen Der p 1 has been detected in both
umbilical cord blood and in amniotic fluid, indicating fetal exposure to allergens (1). Lung
Surfactant Protein-D (SP-D) belongs to the collectin family of carbohydrate-binding proteins,
and has been shown to downregulate allergic hypersensitivity in mice (2,3). Diminished levels of
SP-D at both the fetal and neonatal stage may enhance susceptibility to the development of
allergic diseases.

Aim: To determine whether the presence of SP-D, at the time of primary allergen exposure,
could downregulate allergic hypersensitivity, on subsequent allergen challenge.

Methods: We determined the effects of co-administration of a recombinant fragment of SP-D
(rfhSP-D) with HDM allergens, to BALB/C mice, on the development of allergy on subsequent
(secondary) allergen exposure. All work was undertaken in accordance with UK ethical
guidelines.

Results: In a mouse model of allergic hypersensitivity to the house dust mite
Dermatophagoides
pteronnysinus, treatment with rfhSP-D at the time of primary allergen exposure resulted in
diminished airway hyperresponsiveness and reduced eosiniphilic infiltration into the lungs, on
subsequent allergen challenge. Cultured splenocytes from mice treated with rfhSP-D at the time
of primary allergen exposure also produced increased levels of IFN-γ, and decreased levels of
IL-4, and IL-13 compared to untreated controls, corresponding to a shift in cytokine profile from
Th2 (typical of an allergic response) to Th1. Furthermore, there was a decrease in serum IgE
levels, and increase in serum IgG levels with rfhSP-D treatment, suggesting a role for SP-D in
switching the type of antibody response generated.

Conclusions: These data suggest a novel, protective role for SP-D in allergic sensitization, and a
therapeutic potential of SP-D in the prevention of allergic disease, notably for neonates who are
exposed to allergens and have diminished levels of surfactant proteins.